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Biomedical subjects

S Horn

Publications and source records attributed to S Horn.

At least 55 records · Page 3Linked to original sources
PubMed1996

Isolation, characterization and in vivo analysis of the murine calbindin-D28K upstream regulatory region.

The genomic locus containing the murine calbindin-D28K gene has been isolated and partially characterized. Genomic cloning revealed an exon/intron chromosomal structure very similar to the avian gene previously described. The ability of the calbindin-D28K upstream region to direct cell-specific expression was tested in vivo. Varying lengths of upstream sequence were used to drive expression of lacZ in transgenic mice. Characterization of 23 transgenic mouse lines revealed that even as much as 3.0 kb of upstream sequence was unable to direct expression independently of integration site effects, suggesting the absence of important elements. Despite the small number of expressing transgenic lines and the great variability, there was a tendency of cell specificity of transgene expression exhibited in distinct brain regions. In the cerebellum, Purkinje cell-specific expression was observed with the shortest (1.0 kb) upstream sequence tested. Specificity of transgene expression in Purkinje cells was abolished with longer portions of upstream sequence. The same observation was made for transgene expression in granule cells of the dentate gyrus, while the opposite effect was observed for expression in CA1 hippocampal cells. The absence of any transgenic lines exhibiting appropriate transgene expression in the kidney suggested that the VDREs described previously for the murine calbindin gene are not sufficient to direct kidney expression in vivo. It is concluded that 3.0 kb of calbindin upstream sequence includes the regulatory elements dictating a portion of cell-specificity in the CNS of transgenic mice, albeit lacking regions that allow expression independently of chromosomal effects.

Animals↗
PubMed1996

Spontaneous bacterial peritonitis in a patient with nephrogenic ascites during an episode of acute renal transplant rejection.

Spontaneous bacterial peritonitis (SBP) is a primary infection of asci tes without signs of perforation or penetration. It occurs most often in patients with liver cirrhosis but can also be diagnosed in patients with ascites from other causes. We report a kidney transplant recipient who developed nephrogenic ascites during an episode of acute rejection. The patient complained of fever, abdominal tenderness, and loose stools and showed all of the signs of peritonitis on physical examination. The patient's serum creatinine was elevated, and Duplex sonography of the graft was highly suggestive for acute rejection. Ascites puncture was performed. The ascitic fluid contained 4,000 leukocytes per microliter. No source of infection was detected, so the diagnosis of SBP was made. The patient was treated with ciprofloxacin intravenously and received low-dose steroid pulse therapy. The ascites culture grew Staphylococcus aureus that was highly sensitive to ciprofloxacin. The patient recovered rapidly. We could avoid laparotomy, which is associated with high mortality in patients suffering from SBP. No relapses of SBP occurred. Renal function has improved and remained stable.

Acute Disease↗
PubMed1996

Expression of cell adhesion molecules in lung cancer cell lines.

Cell adhesion mechanisms are among the basic aspects in organism development. Adhesion molecules are involved in the building of complex structures and of association of the tissue. They also mediate as substratum adhesion molecules and are involved in the building of the scaffold. The process of tumor growth and metastasis is a complex cascade of events (FIDLER 1989). For many of these steps the tumor cells must be able to change their degree of adherence. Tumor progression and metastatic dissemination are tightly linked with the ability of the tumor cells to interact with other cells and with the extracellular matrix. The first step of metastasis is the active migration of tumor cells into the surrounding tissue.

Antigens, CD↗
PubMed1995

Membrane glycoprotein modifications of G6PD deficient red blood cells.

In this study, the composition and the role of membrane glycoproteins in phagocytosis were determined in G6PD deficient RBCs. G6PD deficient RBCs were recognized and significantly phagocytosed by murine macrophages, without pre-exposure to oxidants in vivo. Phagocytosis was partially (60%) inhibited by incubating macrophages with either galactose or mannose, or by incubating RBCs with beta-galactosidase, indicating the involvement of lectin-like receptors in the recognition of G6PD deficient RBCs. Membrane glycoproteins on G6PD deficient cells were detected by binding of Con A to both intact RBCs and to purified membrane proteins. The results demonstrated modifications in the glycoprotein pattern of G6PD deficient RBCs compared to untreated controls. These included reduction in the amounts of several high molecular weight glycoproteins and appearance of lower molecular weight bands. These results suggest that G6PD deficient RBCs undergo glycoprotein modifications, which may lead to premature removal from circulation, even in non-acute hemolysis.

Animals↗
PubMed1995

System identification of the low-dose kinetics of p-aminohippuric acid.

The renal clearance of p-aminohippuric acid, due to tubular secretion in addition to glomerular filtration, can only be determined by kinetic experiments. Maximal information can be gained from observed temporal marker concentration profiles by fitting dynamic mathematical models of the processes involved, such as absorption, distribution, and elimination, to the kinetic data. Thereby the values of the system constants, such as fractional elimination or fractional distribution rates, and their accuracy measures are determined by methods which are based firstly on measured time-dependent data elicited in an individual test object by perturbing inputs and secondly, on mathematical formulations of prior knowledge of the underlying physiological system. Such methods of model adaptation are called system identification. In this context a computer-based method of system identification and error estimation for the system constants of two-compartment models matched a dynamic concentration profiles of p-aminohippuric acid is presented. The method is used of single-injection experiments to demonstrate that such a technique is able to correctly estimate the clearance of p-aminohippuric acid if sufficiently long experimental protocols are chosen, and to ascertain the sufficient length of a protocol for an individual subject. The renal clearance of p-aminohippuric acid is known to exhibit concentration-dependence generally, but to achieve its maximal value when low doses are applied. The present study deals with the low-dose kinetics of p-aminohippuric acid.

Adult↗
PubMed1995

Determination of the glomerular filtration rate by identification of sinistrin kinetics.

A computer-based method of system identification and estimation of parameter variance for two-compartment models matched to dynamic sinistrin concentration profiles for the determination of glomerular filtration rate is described. Thereby a procedure for the judgment of the optimal sampling time horizon is presented. Since single-injection techniques are suspected of yielding systematic overestimation of the glomerular filtration rate, a method is demonstrated confirming that such a technique employing sinistrin kinetics can be used to correctly determine the glomerular filtration rate. The validation of the system parameters gained by the single-injection method is made through prediction of the concentration contour under a constant infusion regimen in the same subject on a different occasion. This was performed in healthy controls and in patients with various degrees of renal insufficiency. Upon consideration of the dependence of the clearance estimates and their variances on the protocol duration in test subjects examined from four to ten hours, an adaptive design of the protocol length is developed.

Adult↗
PubMed1995

Computerized support of pressure ulcer prevention and treatment protocols.

Pressure ulcer prevention and treatment protocols were developed and implemented at LDS Hospital. While the protocols were initially implemented "on paper", compliance was not optimum until the hospital's information system was modified to support the clinician in following the new protocols. Preliminary results indicate a significant reduction in the incidence of pressure ulcers.

Clinical Protocols↗
PubMed1994

Regulation of heat-shock protein (hsp70) gene expression by hGH and IL2 in rat Nb2 lymphoma cells.

A comparative study of hGH and IL2 post-signaling effects, as examined by RNA expression (Nb29) and protein levels of the heat-shock protein hsp70, was performed in a hormone-dependent rat lymphoma cell line, Nb2-11C. Optimal doses of hGH or IL2 increased Nb29 expression in a dose-dependent manner. Addition of both mitogens to cell cultures affected Nb29 expression and mitogenesis synergystically, indicating a possible interaction between the post-receptoral mechanisms of these mitogens. Pretreatment of the cells with cholera toxin (CT) inhibited Nb29 expression, protein levels and mitogenesis of hGH- or IL2-induced cells up to 50%, indicating the involvement of Gs-proteins in the post-signaling processes of both hGH and IL2. Incubation of cell cultures with low concentrations of pertussis toxin (IAP) (0.01 ng/ml) markedly increased Nb29 expression in hGH but not in IL2-induced cells, suggesting specific involvement of the Gi-protein in post-signaling processes of hGH-induced cells. Addition of the PKC activator 12-O-tetra-decanoyl phorbol ester (TPA) to control cell cultures markedly increased the expression of Nb29 RNA levels but not mitogenesis, indicating that induction of these proteins in the cells is not sufficient for cell proliferation. Furthermore, incubation of hGH- or IL2-induced cells with the potent PKC inhibitor staurosporin (ST) decreased the levels of Nb29 in both hGH- and IL2-induced cells, although the effect of the mitogens differed significantly in their inhibition slopes. These results indicate that activation of PKC is one of the signaling pathways differentially involved in hGH and IL2 stimulation of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1994

Anti-nuclear, anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies in HIV-infected individuals.

Many autoantibodies have been described in HIV-infected individuals. We have examined the incidence, associations and prognostic significance of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies in individuals with HIV infections. One hundred and five patients, with asymptomatic infections (n = 37), AIDS-related complex (n = 32) or AIDS (n = 36) were studied. Plasma from 24 of these (23%) were positive for ANA: most demonstrated speckled fluorescence (n = 21) and were of low titre (1+ in 18). ANCA were demonstrated by IIF in 18 individuals (17%) and all fluorescent patterns were seen; 6 of these plasma were also positive in the ELISAs for antibodies to proteinase 3, myeloperoxidase or elastase. Thirteen plasma were positive for ANCA in the neutrophil cytoplasm ELISA; 10 of these were also positive in the specific ELISAs. A total of 30 plasma bound to proteinase 3, myeloperoxidase or elastase in specific ELISAs, in 6 cases with 2 specificities. Finally, 18 plasma (17%) contained anti-GBM antibodies by ELISA, but none of 4 plasma tested in inhibition assays was specific. ANA, ANCA and anti-GBM antibodies were not uncommon in HIV-infected individuals but the presence of these antibodies was not associated with the clinical manifestations of the corresponding autoimmune diseases. In addition, there was no correlation between the demonstration of these antibodies and the immunological status of the individual (apart from a correlation between CD4 counts less than 400/microliters with anti-GBM antibodies), the presence of an opportunistic infection, the development of malignancy or reduced survival. Some of these antibodies may arise from polyclonal activation, or be due to "sticky" serum since we have shown that the presence of anti-GBM antibodies correlated with the demonstration of ANCA by ELISA. These antibodies are not more common in hypergammaglobulinemic plasma but some may be due to heat-treatment of the plasma. The clinician caring for HIV-infected individuals needs to be aware of these "false-positive" antibody results.

Adult↗
PubMed1993

Constitutive transcriptional activator of Epidermodysplasia verruciformis-associated human papillomavirus 8.

Human papillomavirus (HPV) 8 belongs to the HPV types frequently associated with skin cancers of Epidermodysplasia verruciformis (EV)-patients. There are 33 nucleotides (M33 motif) in the 5'-part of the non-coding regulatory region of HPV8, which appear highly conserved among EV-specific HPVs and are consistently followed by an AP1 binding site. These sequences were shown to constitute an essential activator of transcription driven by the HPV8 late promoter P7535. The M33/AP1 element displayed properties of a constitutive enhancer, being also able to stimulate the activity of the heterologous thymidine kinase promoter in a position-independent manner. No protein binding could be detected within the 5'-part of the M33/AP1 region, which contributed significantly to the overall activity of the HPV8 enhancer. As shown by DNasel-footprinting, the central and the 3'-part of the enhancer region were involved in interactions with nuclear proteins. Three specific complexes could be observed in gel retardation tests with nuclear extracts from epithelial cells. One of these interactions involved the AP1 protein. Analysis of deletion and point mutations revealed binding of the AP1 protein to be essential for transcriptional activation, but DNA-protein interactions within M33 were important for maximal stimulation. The response to the phorbol ester TPA also required a cooperation of M33 and AP1.

Base Sequence↗
PubMed1993

The influence of lecithin on plasma choline concentrations in triathletes and adolescent runners during exercise.

An investigation was carried out on the effect of lecithin (phosphatidylcholine, 90%) on the plasma choline concentrations during continuous strain in 10 top level triathletes (4 women and 6 men), trial I, and 13 excellent adolescent runners (3 girls and 10 boys), trial II. Venous blood, collected before and immediately after the race, was separated and plasma was assayed by an improved high performance liquid chromatography method for choline. Each study comprised three experiments. In trial I the triathletes performed two periods of bicycle exercise each lasting 2 h at an average speed of 35 km.h-1, and in the second study (trial II) the subjects were subjected to severe physical stress on two occasions during cross-country races of durations between 30-60 min according to their ages. The participants received either a placebo or 0.2 g lecithin.kg body mass-1, 1 h before each exercise. As a control the same dose of lecithin was administered without any exercise (both trials I and II). Bicycle exercise without lecithin supply decreased plasma choline concentrations in all the triathletes, on average by 16.9% (P < or = 0.01). When lecithin was given before exercise, average plasma choline concentrations remained at the same level as the initial values. The supply of lecithin without exercise led to a significant increase of the plasma choline concentrations, on average by 26.9% (P < or = 0.01). In trial II, when running without a supply of lecithin, the mean plasma choline concentrations in the adolescent runners remained stable which may have been due to the duration of the physical stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

In vitro expansion and analysis of T lymphocyte microcultures obtained from the vaccination sites of cancer patients undergoing active specific immunization with autologous Newcastle-disease-virus-modified tumour cells.

In order to understand further the effects of Newcastle-disease-virus(NDV)-modified tumour vaccines we investigated the feasibility of isolating lymphocytes from the site of injection of patients undergoing postoperative active specific immunization (ASI) with autologous NDV-modified tumour cells. Delayed-type-hypersensitivity(DTH)-like reactions from five cancer patients were surgically removed, minced and the tissue particles were digested with collagenase and DNase. Lymphoid cells recovered were expanded in a highly efficient limiting-dilution analysis system optimized for T cell growth [Moretta et al. (1983) J Exp Med 157: 743] and lymphocyte microcultures (clonal probability > 0.8) could be grown for up to 1 year. Analysis of the microcultures for phenotype and function showed that the majority were positive for CD4 (92%) and TCR alpha beta (96%). Concanavalin-A-induced production of interleukin-2 (IL-2), IL-6, interferon gamma and tumour necrosis factor alpha was detected in more than 70% of the microcultures. Lectin-dependent cytotoxicity was only very rarely observed. The general characteristics of the microcultures obtained support the notion of a DTH-like reaction taking place at the site of tumour cell challenge. The possibility of in vitro expansion and cultivation of T lymphocytes from ASI vaccination sites should help to elucidate further the role of these cells in active specific immunization against autologous tumour cells.

Cells, Cultured↗